Influence of concurrent oral calcium carbonate supplementation on steady-state pharmacokinetics of once daily oral raltegravir in persons with HIV: a protocol for a prospective open-label non-randomised study in Canada

Introduction
Raltegravir is a potent HIV-integrase strand transfer inhibitor (INSTI). Despite its strong activity against HIV-1 strains resistant to other antiretroviral drug classes, it is usually used in combination with other antiretroviral drugs due to the empirical requirement for anti-HIV drug combinations to ensure effective anti-retroviral therapy (ART). As an early-arriving INSTI, raltegravir is clinically familiar for its safety, tolerability and treatment effectiveness. High-dose calcium carbonate formulated as an antacid (as opposed to a supplement formulation) taken orally together with raltegravir is known to reduce systemic raltegravir exposure due to chelation and reduced absorption. This study aims to assess the effect of daily calcium carbonate antacid as TUMS Ultra Strength (US) administration in lower doses, as currently used for oral calcium supplementation, on the steady-state pharmacokinetics (PKs) of once-daily oral raltegravir.

Methods and analysis
This is an open-label, three-treatment series in three periods in a single group, fixed-sequence PK study in 12 healthy adult volunteers with HIV on ART. Subjects will take 1200 mg of raltegravir single QD oral dose alone for 7 days (period one), then raltegravir 1200 mg with calcium carbonate 500 mg from day 8 to day 14 (period two) and raltegravir 1200 mg with calcium carbonate 1000 mg from day 15 to day 22 (period three). We will conduct serial PK sampling from observed dosing on days 7, 14 and 21, with 24-hour PK sampling scheduled for days 8, 15 and 22. Follow-up will continue until day 51.

Ethics and dissemination
This study will adhere to the ICH GCP Guidelines and the Declaration of Helsinki. Ethics approval was obtained from the Ottawa Health Science Network Research Ethics Board under study ID 20190750–01 hour. Informed consent will be obtained from all participants prior to enrolment. This protocol will be published in a peer-reviewed journal prior to the study’s completion and closure. Results generated from this activity will also be reported in a peer-reviewed journal.

Trial registration number
NCT04258475.

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Association between anti-Mullerian hormone levels and age in women with endometriosis: insights from a population-based study

Background
While previous studies have shown an association between anti-Mullerian hormone (AMH) levels and endometriosis, there are limited data on the relationship between AMH levels and age among women with endometriosis.

Objectives
The present study aimed to investigate the associations between age and AMH levels in women with and without endometriosis.

Design and setting
A cross-sectional, population-based study using data from the ongoing Tehran Lipid and Glucose Study.

Participants
A total of 1005 eligible reproductive-age women were selected. These participants were categorised into two groups: women with confirmed endometriosis (n=305) and controls (n=700).

Interventions
None.

Outcome measures
Association between AMH levels and age among women with endometriosis and healthy controls, using linear, quadratic and segmented regression analyses.

Results
A total of 1005 women aged 18–48 years participated in the study, including 305 (30.3%) with endometriosis and 700 (69.7%) healthy controls. Women with endometriosis had significantly lower AMH levels compared with healthy controls (1.99±1.42 vs 2.30±1.61 ng/mL; p=0.029). In healthy controls, an increase of 1 year was associated with –0.15 ng/mL of AMH (95% CI: –0.17 to –0.14). Segmented regression identified a threshold at 27 years (1.92), with a sharper decline below this age (slope: –0.35, 95% CI: –0.47 to –0.23; p

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[Articles] Efficacy and safety of narlumosbart, an anti-RANKL monoclonal antibody, in postmenopausal women with osteoporosis: a multi-center, randomized, double-blind, placebo- and active-controlled, phased II study

In this phase II trial of postmenopausal women with osteoporosis, narlumosbart demonstrated superiority over placebo in increasing BMD at 12 months following administration at 6-month intervals, with a tolerable safety profile in the short term, consistent with that of anti-RANKL monoclonal antibodies.

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Evaluation of a virtual reality-directed brain-gut behavioural treatment inpatient program for patients with inflammatory bowel disease: protocol for a pilot feasibility trial

Introduction
Pain is one of the most bothersome symptoms that affects patients with inflammatory bowel disease (IBD) but is often inadequately treated. Inadequate pain control in the inpatient setting not only impacts patients’ experience but increases opioid use and hospital length of stay. Opioids are often considered first-line treatment for severe pain but are associated with significant morbidity and mortality in IBD. Non-steroidal anti-inflammatory drugs are a non-opioid analgesic option, but concerns regarding their contribution to IBD flares have limited their use. Brain-gut behavioural therapies (BGBT), such as cognitive behavioural therapy, meditation and gut-directed hypnotherapy, are effective for pain management and have a role in the treatment of IBD symptoms. However, the use of BGBT in IBD is challenging, given limited access to behavioural health specialists, especially in the inpatient setting. Virtual reality (VR)-directed BGBT programmes can bridge this gap and enhance pain treatment for inpatients with IBD. Therefore, in this study, we aim to establish feasibility and acceptability for a VR-directed BGBT inpatient programme for patients with IBD.

Methods and analysis
We will recruit 40 patients with IBD who are hospitalised at Michigan Medicine and who endorse IBD-related pain. We will assess patient-reported outcomes (pain rating, IBD-specific symptoms, perceived stress, mood) before and after treatment, cumulative inpatient analgesic requirements and hospital length of stay. Our primary objective will be to establish intervention feasibility defined by the frequency and percentage of enrolled participants that use the VR-directed BGBT inpatient intervention in any capacity. Our secondary objective will be to evaluate intervention acceptability by conducting semistructured interviews with study participants. We will also explore the preliminary effectiveness of VR-directed BGBT on patient-reported outcomes and healthcare utilisation as compared with historic controls.

Ethics and dissemination
The study was approved by the institutional review board of the University of Michigan Medical School on 10 October 2023 (HUM00240999). All human subjects will be required to sign an informed consent document prior to study participation. Study findings will be reported through peer-reviewed publication.

Trial registration number
NCT06188793.

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